Our aim is to understand the mechanisms of some of the functions of the excitable membrane and cilia by genetic dissection. This is done by producing molecular lesions with mutagenesis and analyzing the resultant effects on behavior, electrophysiology and the ultrastructure. Our choice of material greatly simplified such a study. Paramecia are ciliated unicells with excitable membranes capable of generating action potentials. Using the relatively stereotyped locomotor behavior as the indicator of the state of membrane and ciliary activity, and taking advantage of the presence of autogamy in Paramecium aurelia, mutants can be selected which carry molecular lesions affecting membrane activity or ciliary structure. Membrane mutants have been isolated and studied behaviorally, genetically, and electrophysiologically. The first case of genic deletion of action potential in a known cell has been demonstrated in our system in the case of the mutant "Pawn". We aim to continue this fruitful interdisciplinary approach. Specifically, we propose to screen for other behavioral mutants with membrane or ciliary defects using a proven method and two newly devised methods based on galvanotaxis and the use of chemicals with known effects on membrane and ciliary activity. We also plan to continue the genetic and bioelectric analysis of the mutants on hand, especially the Na-specific mutants, "Fast-2" and "Paranoiac". A small part of our effort will be directed to the analysis of the ultrastructure of ciliary mutants. The search for the defective gene products which are correlated with the modified electrical properties and behavior will be conducted in collaboration with other laboratories so as to make maximum use of the experience of the principal investigator in genetics and electrophysiology. BIBLIOGRAPHIC REFERENCES: Hansma, H.G. and C. Kung (1975) Studies of the cell surface of Paramecium, Ciliary membrane proteins and immobilization antigens. Biochem. J. 152, 523-528. Satow, Y., H.G. Hansma and C. Kung (1976) The effect of sodium on "Paranoiac" - a membrane mutant of Paramecium. Comp. Physiol. and Biochem. (in press).